Regular exercise is a cornerstone of the primary and secondary prevention of cardiovascular diseases (CVDs), yet the mechanisms underlying its cardioprotective effects remain incompletely understood. Emerging evidence indicates that dysfunction of the brain–heart axis is closely involved in the onset and progression of CVDs, whereas exercise may exert cardiovascular protection, at least in part, by modulating this bidirectional regulatory network. This review summarizes the pathophysiological significance of brain–heart axis dysregulation in CVDs and systematically discusses the potential mechanisms through which exercise regulates this axis to alleviate CVDs. We further examine how exercise prescription-related variables may differentially influence brain–heart axis regulation and address the potential risks associated with excessive exercise. Finally, we highlight future directions for translating these mechanistic insights into precision exercise medicine. Overall, this review provides an updated framework for understanding how exercise modulates the brain–heart axis in CVDs and offers new perspectives for their prevention and treatment.

Regular exercise and physical activity are beneficial in reducing the risk and progression of ischemic stroke. However, the underlying physiological mechanisms by which exercise confers these protective effects remain incompletely understood. Disruption of mitochondrial homeostasis is key contributors to the pathophysiology of ischemic stroke. Exercise training effectively attenuates the onset and progression of ischemic stroke by significantly maintaining mitochondrial homeostasis, including improving mitochondrial biogenesis, balancing mitochondrial dynamics, maintaining mitochondrial redox, promoting mitophagy and mitochondrial transport. This review systematically summarizes the beneficial effects of exercise in the context of ischemic stroke and highlights the critical link between mitochondrial homeostasis disruption and stroke pathology. By providing a detailed analysis of the underlying molecular mechanisms, this study offers novel insights into exercise-based therapeutic strategies for ischemic stroke.

Exercise is an important non-pharmacological intervention for the prevention and management of diabetes and its cardiovascular complications; however, the underlying mechanisms by which exercise confers cardiometabolic protection remain incompletely understood. Diabetic cardiomyopathy (DCM) is a major cardiovascular complication of diabetes, characterized by progressive myocardial structural and functional abnormalities associated with oxidative stress, dysregulated lipid metabolism, chronic inflammation, and miochondrial dysfunction. Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has emerged as a potential pathological link between metabolic disturbances and myocardial injury in DCM. Accumulating evidence suggests that exercise may modulate ferroptosis through multiple interconnected mechanisms, including restoration of iron homeostasis, suppression of lipid peroxidation, enhancement of endogenous antioxidant defenses, and improvement of mitochondrial function and quality control, thereby contributing to myocardial protection. In this review, we systematically summarize the cardioprotective benefits of exercise in the context of DCM and critically discuss the potential associations between exercise characteristics, including exercise modality, intensity, duration and the regulation of ferroptosis. By integrating current evidence on the molecular mechanisms underlying exercise-mediated ferroptosis regulation, this review provides a mechanistic framework for understanding how exercise may counteract ferroptosis in DCM and highlights the potential of ferroptosis-informed, precision exercise strategies for the prevention and management of diabetic cardiomyopathy.

Exercise is one of the safe and effective methods to improve obesity and its complications, but the mechanism has not been fully elucidated. Sestrin2 (SESN2) is a stress-induced protein that protects cells from stress damage. The role and mechanism of SESN2 in the improvement of obesity-induced cardiac dysfunction by exercise are still unclear. Male C57BL/6J mice were used to prepare a high-fat diet-induced obesity mouse model and conducted aerobic exercise training. After training, echocardiography was used to evaluate the cardiac function of mice, and HE and Masson staining were used to assess the extent of cardiac damage. Cell experiments were conducted using the H9C2 cell line derived from embryonic rat hearts, with the intervention of palmitic acid ester and exogenous SESN2. We detected indicators related to myocardial cell damage, fibrosis, inflammation, and oxidative stress, as well as the activation level of the AMPK-PGC-1α signaling pathway. The results showed that aerobic exercise significantly inhibited myocardial fibrosis, inflammation, oxidative stress, and cell damage in HFD mice, upregulated cardiac SESN2 expression, and activated the AMPK-PGC-1α signaling pathway. Cell experiments have found that exogenous SESN2 pretreatment alleviates palmitate-induced injury, inflammation, and oxidative stress in H9C2 cardiomyocytes, and activates the AMPK-PGC-1α signaling pathway. This indicates that aerobic exercise significantly upregulates the expression of SESN2 and activates the AMPK-PGC-1α signaling pathway, which is potentially involved in alleviating myocardial inflammation, oxidative stress, cardiac fibrosis and cardiac dysfunction in HFD mice.